Ambrisentan
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| Non-proprietary name | Ambrisentan | |||||||||||||||||||||
| other names |
( S ) -2- (4,6-Dimethylpyrimidin-2-yloxy) -3-methoxy-3,3-diphenylpropionic acid ( IUPAC ) |
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| Molecular formula | C 22 H 22 N 2 O 4 | |||||||||||||||||||||
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| Mechanism of action |
Endothelin is selectively displaced by its ET 1A receptors, resulting in vascular dilatation and (pulmonary) blood pressure lowering |
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| Molar mass | 378.42 g mol −1 | |||||||||||||||||||||
| Melting point |
181 ° C |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||||||||||||||
Ambrisentan is a drug from the group of endothelin receptor antagonists . It is used to treat a rare form of high blood pressure in which blood pressure is increased in the blood vessels through which blood flows from the heart to the lungs (pulmonary hypertension , pulmonary arterial hypertension (PAH) WHO functional classes II and III).
He is under the area of application for this trade names Volibris ® (manufacturer GlaxoSmithKline (GSK)) since 2008 in the European Union and Switzerland approved .
Ambrisentan, like the endothelin receptor antagonists bosentan and sitaxentan , is classified as an orphan drug .
pharmacology
Mechanism of action
Ambrisentan displaced as antagonist the endothelin -1, the most potent known endogenous Blutgefäßkonstringenz, selectively from its ET 1A receptors and therefore cancels the effect of endothelin-1, so that the vessels dilate and (pulmonary) so the increase caused by the endothelin of Blood pressure is counteracted and there is a (pulmonary) decrease in blood pressure. The selectivity results in an advantage over the unselective bosentan, since the effects caused by the ET 1B receptors, the production of the vasodilators nitric oxide (NO) and prostacyclin, remain unaffected and can thus cause additional dilation . This also counteracts the changes in the blood vessels - remodeling - caused by the endothelin .
Side effects
Side effects of interfering with blood pressure regulation can include headaches, reddening of the skin and peripheral edema, disorders in the gastrointestinal tract (nausea and abdominal pain) and also sinusitis-like symptoms with a blocked nose are possible.
Contraindications
Contraindications are pregnancy and liver dysfunction associated with increased liver transaminases. In July 2012, the manufacturer GSK pointed out in a Rote-Hand-Brief that ambrisentan should not be used in patients with idiopathic pulmonary fibrosis (IPF) .
Studies
Phase III studies - ARIES-1 and ARIES-2
Web links
- Summary of the Characteristics of Volibris as of April 21, 2008 on the European Medicines Agency EMEA website (PDF file; 251 kB)
Individual evidence
- ↑ J. Haneef, R. Chadha, V. Gupta, SK Mandal: Novel polymorph of ambrisentan: Characterization and stability. In: J. Pharm. Biomed. Anal. 153, 2018, pp. 102-109, doi: 10.1016 / j.jpba.2018.02.006 .
- ↑ There is not yet a harmonized classification for this substance . A labeling of (+) - (2S) -2 - [(4,6-dimethylpyrimidin-2-yl) oxy] -3-methoxy-3,3-diphenylpropanoic acid in the Classification and Labeling is shown, which is derived from a self-classification by the distributor Inventory of the European Chemicals Agency (ECHA), accessed on December 16, 2019.
- ↑ Entry on ambrisentan at TCI Europe, accessed on February 16, 2020.
- ↑ a b c ABDA database (as of July 17, 2008) of DIMDI .
- ^ A b c Pharmaceutical newspaper. No. 27, July 3, 2008, p. 24 ff.
- ↑ Rote-Hand-Brief: VOLIBRIS ® (ambrisentan) must not be used in patients with idiopathic pulmonary fibrosis (IPF). (PDF; 981 kB) retrieved from the website of the Drugs Commission of the German Medical Association (AkdÄ).
